Cardiac Specializations, Aging, CHF, Congenital Heart Dz, Ischemic Heart Dz

Question 1

Atrial myocytes have storage granules that contain ANP which promotes arterial vasodilation and stimulates natriuresis and diuresis, which is beneficial in the setting of ___ and ____

Answer 1

HTN; CHF

Question 2

Due to their thin structure, heart valves derive most of their nourishment via _____; normal leaflets and cusps’ vessels are limited to the ____ portions

Answer 2

Diffusion; proximal

Question 3

3 general types of damage that occur in valves

Answer 3

Collagen —> mitral prolapse

Nodular calcification —> calcific aortic stenosis

Fibrotic thickening —> rheumatic heart dz

Question 4

During ventricular diastole, closure of the ____ valve leads to _____

Answer 4

Aortic; blood flow to myocardium

Question 5

Describe cardiac stem cells

Answer 5

Bone marrow derived precursors and stem cells are present in the myocardium but only replace about 1% each year — thus no significant recovery in zone of necrosis

Question 6

Effects of aging on myocardium and chambers of the heart

Answer 6

Increased LV chamber size, increased left atrial cavity size, sigmoid shaped ventricular sepum

Increased epicardial fat

Myocardium changes include lipofuscin, basophilic degeneration, and possible amyloid deposition

Question 7

Effect of aging on heart valves

Answer 7

Aortic and mitral valves undergo annular calcification

Fibrous thickening

Mitral leaflets buckle towards left atrium —> increased left atrium size

Lambl excrescences = small filiform processes that form on closure lines of aortic and mitral valves, probably resulting from organization of small thrombi

Question 8

Vascular changes that occur with aging

Answer 8

Coronary atherosclerosis

Stiffening and dilation of the aorta, elastic fragmentation and collagen accumulation

Question 9

____ occurs when the heart is unable to pump blood at a rate to meet peripheral demand, OR can only do so with increased filling pressure

May result from loss of myocardial contractile function (systolic dysfunction) or loss of ability to fill the ventricles during diastole (diastolic dysfunction)

Answer 9

CHF

Question 10

Cardiac myocytes become hypertrophic in the setting of sustained pressure or volume overload (such as in ____ or _____), or in the setting of sustained ____ signals (such as beta-adrenergic stim)

Answer 10

Systemic HTN; aortic stenosis

Trophic

Question 11

In the setting of ______ overload hypertrophy, myocytes become thicker and the LV increases in thickness concentrically

In the setting of _____ overload hypertrophy, myocytes elongate and ventricular dilation is seen

Answer 11

Pressure

Volume

Question 12

Hypertrophy of myocytes isn’t accompanied by a matching increase in blood supply despite increased energy demand — thus what is a major complication of cardiac hypertrophy?

Answer 12

Ischemia-related decompensation

Question 13

Left sided heart failure can be systolic or diastolic; it is most commonly a result of what conditions?

Answer 13

Myocardial ischemia

HTN

Left-sided valve dz

Primary myocardial dz

Question 14

What are the clinical effects of left sided heart failure? What causes them?

Answer 14

Clinical effects include paroxysmal nocturnal dyspnea, elevated pulmonary capillary wedge pressure, pulmonary congestion (cough, crackles, wheezes, blood-tinged sputum, tachypnea), restlessness, confusion, orthopnea, tachycardia, exertional dyspnea, fatigue, cyanosis

These occur d/t decreased tissue perfusion and congestion in pulmonary circ

Question 15

Left-sided heart failure is characterized by left ventricular hypertrophy. Left ventricular dysfunction leads to left atrial dilation, resulting in what potential complications?

Answer 15

Atrial fibrillation, stasis, thrombus

Question 16

The decreased ejection fraction associated with left sided heart failure may result in what complications concerning the kidneys?

Answer 16

Decreased EF —> decreased glomerular perfusion —> renin release —> increased volume

Prerenal azotemia

Question 17

Histologic finding with left-sided heart failure

Answer 17

Heart failure cells = hemosiderin-laden macrophages

Question 18

Advanced CHF may lead to decreased cerebral perfusion —> ____ ____

Answer 18

Hypoxic encephalopathy

Question 19

Most common cause of right sided heart failure

Answer 19

Left sided heart failure

Question 20

Isolated right sided heart failure may result from what conditions?

Answer 20

Anything that causes pulmonary HTN — parenchymal lung dz, primary pulmonary HTN, or pulmonary vasoconstriction

Question 21

Clinical features of right-sided heart failure

Answer 21

In primary right sided failure, pulmonary congestion is minimal

The venous system is markedly congested, leading to:
Liver congestion (nutmeg liver)

Splenic congestion (splenomegaly)

Effusions involving peritoneal, pleural, and pericardial spaces

Edema, especially in dependent areas (e.g., ankles)

Renal congestion

Other Symptoms: fatigue, distended jugular vv, anorexia and complaints of GI distress, weight gain

Question 22

Sporadic genetic abnormalities are the major known causes of congenital heart disease. What are the major examples?

Answer 22

Turner syndrome, trisomies 13, 18, and 21

The single MOST COMMON genetic cause of congenital heart disease is TRISOMY 21 — about 40% of pts with Down syndrome have at least one heart defect

Question 23

Describe heart defects associated with trisomy 21

Answer 23

Usually derived from second heart field (arterioventricular septae) — most commonly defects of the endocardial cushion, including ostium primum, ASDs, AV valve malformations, and VSDs

Question 24

What congenital heart diseases are associated with the Notch pathway?

Answer 24

Bicuspid aortic valve (NOTCH1)

Tetralogy of Fallot (JAG1 and NOTCH2)

Question 25

______ mutations are associated with Marfan syndrome which is associated with ____ defects and aortic aneurysms

Answer 25

Fibrillin; valvular

Question 26

Most common type of congenital cardiac malformation

Answer 26

Ventricular septal defect (VSD)

Question 27

Genes associated with the nonsyndromic congenital heart defects

Answer 27

ASD or conduction defects (NKX2.5) ASD or VSD (GATA4) Tetralogy of fallot (ZFPM2 or NKX2.5) Note that tetralogy of fallot when associated wtih alagille syndrome is associated with JAG1 or NOTCH2

Question 28

What type of shunt is considered the most common congenital heart dz?

Answer 28

Left-to-right shunts — including ASD, VSD, and PDA

Question 29

Of the common congenital left-to-right shunts, the _____ causes increased outflow volume from the RV and pulmonary system, while the ____ and _____ both cause increased pulmonary blood flow and pressure

Answer 29

ASD; VSD, PDA

Question 30

T/F: Atrial septal defects tend to be rapidly fatal

Answer 30

False — ASDs are usually asymptomatic until adulthood

Question 31

3 types of atrial septal defects

Answer 31

Secundum ASD: 90% of all ASDs — occurs at center of atrial septum; may be multiple or fenestrated Primum anomaly: 5% of all ASDs — occurs adjacent to AV valves; often associated with AV valve abnormalities and/or VSD Sinus venosa defects: 5% of all ASDs — occurs near entrance of SVD; can be associated with anomalous pulmonary venous return to the R atrium

Question 32

Clinical consequences of congenital left to right shunting

Answer 32

Left-to-right shunting causes volume overload on the right side, which may lead to pulmonary HTN, right heart failure, or paradoxical embolization May be closed surgically with normal survival

Question 33

80% of PFOs close permanently by 2 y/o, in the remaining 20% the flap can open if there is an increase in ____-sided pressure, inducing brief periods of ___-___ shunting, such as with pulmonary HTN, bowel movement, coughing, or sneezing. One of the complications of most concern is the possibility for ________ _______

Answer 33

Right; R-L; paradoxical embolus

Question 34

T/F: the majority of VSDs are infundibular (occuring below pulmonary valve or within muscular septum)

Answer 34

False - 90% of VSDs are membranous

Question 35

Clinical effects of a VSD

Answer 35

Effects depend on size and presence of other heart defects (those that manifest as children are often associated with other heart anomalies) Many small VSDs close spontaneously Large VSDs may cause significant shunting, leading to right ventricular hypertrophy and pulmonary HTN which can ultimately reverse flow through the shunt, leading to cyanosis

Question 36

Patent ductus arteriosus may fail to close when infants are ______, and/or have defects associated with increased ______ pressure (such as with VSD)

Answer 36

Hypoxic; pulmonary vascular

Question 37

Major clinical findings with patent ductus arteriosus

Answer 37

PDA produces harsh, machine-like murmur Effect is further determined by shunt’s diameter — large shunts can increase pulmonary pressure and eventually shunt reversal and cyanosis

Question 38

Cyanosis early in postnatal life may occur as a result of what cyanotic congenital heart diseases?

Answer 38

``` Tetralogy of fallot (most common) Transposition of the great arteries Persistent truncus arteriosus Tricuspid atresia Total anomalous pulmonary venous connection ```

Question 39

Clinical presentation of a child with TOF

Answer 39

Squatting Cyanosis Clubbing Syncope [clinical severity depends on degree of subpulmonary stenosis which obstructs the RV outflow tract. Mild stenosis causes L to R shunt. Classic TOF is R to L shunting with cyanosis. Most infants are cyanotic from birth, or soon thereafter]

Question 40

4 cardinal pathologic features of TOF

Answer 40

VSD Obstruction of RV outflow tract Aorta overrides the VSD RV hypertrophy (heart is enlarged and “boot-shaped” because of this)

Question 41

Describe prognosis and comorbidities associated with transposition of the great vessels

Answer 41

Transposition of the great vessels results in 2 separate circuits and is incompatible with life unless a shunt is present for mixing of blood from the 2 circuits Approximately 1/3 have a VSD 2/3 have a PFO or PDA Right ventricule becomes hypertrophic (supports systemic circulation), and the left ventricle atrophies Without surgery, pts will die in a few months

Question 42

Differentiate presentation of coarctation of the aorta (narrowing of the aorta) in infants vs. adults

Answer 42

Infantile form: generally seen WITH a PDA, manifests at birth; may produce cyanosis in lower half of the body Adult form: generally seen WITHOUT a PDA; usually asymptomatic but can see hypERtension in UEs and hypOtension in LEs. LEs may also exhibit coldness and claudication; may eventually see concentric LV hypertrophy [regardless of type, degree of narrowing is variable with variable clinical effect — clinical severity depends on degree of stenosis and patency of ductus arteriosus]

Question 43

What patient populations are at higher risk for coarctation of the aorta?

Answer 43

Males > females Turner syndrome (45,XO)

Question 44

Ischemic heart dz results from insufficient perfusion to meet metabolic demands of the myocardium. Blood to the myocardium is supplied by the coronary arteries, so any disruption of coronary flow may result in ischemia. Ischemia may lead to what complications?

Answer 44

Myocardial infarction Angina pectoris Chronic IHD with heart failure Sudden cardiac death

Question 45

Ischemic heart dz is the leading cause of death in the US, and >90% are secondary to _______

Answer 45

Atherosclerosis [associated with chronic vascular occlusion; acute plaque change —> thrombus]

Question 46

Transient, often recurrent chest pain induced by myocardial ischemia insufficient to induce myocardial infarction

Answer 46

Angina pectoris

Question 47

3 clinical varians of angina pectoris

Answer 47

Stable angina Prinzmetal variant angina Unstable (or “crescendo”) angina

Question 48

Describe stable angina variant

Answer 48

Stenotic occlusion of coronary artery “Squeezing” or burning sensation, relieved by rest or vasodilators Induced by physical activity or stress

Question 49

Describe prinzmetal variant angina

Answer 49

Episodic coronary a. spasm, relieved with vasodilators Unrelated to physical activity, HR, or BP

Question 50

Describe unstable (crescendo) variant angina

Answer 50

Frank pain, increasing in frequency, duration, and severity at progressively lower levels of physical activity, eventually even at rest Usually rupture of atherosclerotic plaque with partial thrombus ~50% may have evidence of myocardial necrosis; ACUTE MI MAY BE IMMINENT

Question 51

In terms of myocardial infarction, age distribution and risk factors mirror those of atherosclerosis in general because nearly 90% of infarcts are caused by an atheromatous plaque. What are some other potential causes of MI?

Answer 51

Embolus Vasospasm Ischemia secondary to vasculitis, shock, or other hematologic abnormalities

Question 52

Classic presentation of MI

Answer 52

Prolonged CP (>30 min) described as crushing, stabbing, squeezing, tightness, radiating down left arm or left jaw Diaphoresis Dyspnea N/V HOWEVER - up to 25% are asymptomatic

Question 53

The location, size, and features of an acute MI depend on what factors?

Answer 53

The site, degree, and rate of occlusion of the artery Size of the area perfused Duration of the occlusion Metabolic and oxygen needs of the area at risk Extent of collateral blood flow Presence of arterial spasm

Question 54

Physiologic changes that occur following severe myocardial ischemia How long until onset of irreversible injury?

Answer 54

Onset of ATP depletion within seconds and loss of contractility within 2 minutes; increase in lactic acid Onset of irreversible injury around 20minute mark; microvascular injury takes about 1 hr

Question 55

T/F: upon occlusion of coronary artery, the area of necrosis begins in the area directly adjacent to the occluded vessel first

Answer 55

False — the necrotic area begins in region of endocardium furthest from occluded vessel and extends back toward area of obstruction

Question 56

Most common coronary vessels occluded in acute MI and the subsequent areas of infarction

Answer 56

LAD (40-50%) —> apex, LV anterior wall, anterior 2/3 of septum RCA (30-40%) —> RV free wall, LV posterior wall, posterior 1/3 of septum LCX (15-20%) —> LV lateral wall

Question 57

What occlusion locations result in transmural infarcts?

Answer 57

Permanent occlusion of LAD branch Permanent occlusion of left circumflex branch Permanent occlusion of RCA (or its posterior descending branch)

Question 58

What occlusion locations result in non-transmural infarcts?

Answer 58

Transient/partial obstruction in coronary vessels —> subendocardial infarct Global hypotension —> circumfirential subendocardial infarct Small intramural vessel occlusions —> microinfarcts

Question 59

Gross features, light microscope, and electron microscope findings immediately following MI

Answer 59

Gross features: none Light microscope: none Electron microscope: relaxation of myofibrils, glycogen loss, mitochondrial swelling

Question 60

Gross features, light microscope, and electron microscope findings within 30 minutes—4hours following an MI

Answer 60

Gross features: none Light microscope: usually none; variable waviness of fibers at border Electron: sarcolemmal disruption, microchondrial amorphous densities

Question 61

Gross features and light microscope findings within 4-12 hours of acute MI

Answer 61

Gross features: occasional dark mottling Light micro: early coagulation necrosis; edema; hemorrhage

Question 62

Gross features and light microscope findings within 12 hours—3 days of acute MI

Answer 62

Gross features: dark mottling with yellow-tan infarct center Light micro: ongoing coagulation necrosis; pyknosis of nuclei, myocyte HYPEREOSINOPHILIA, marginal contraction band necrosis; early neutrophilic infiltrate. Within 1-3 days there is loss of nuclei and striations + brisk interstitial infiltrate of NEUTROPHILS

Question 63

Gross features and light microscope findings within 3-10 days of acute MI

Answer 63

Gross features: hyperemic border; central yellow-tan softening. Within 7-10 days becomes maximally yellow-tan and soft with depressed red-tan margins Light micro: beginning disintigration of dead myofibers with dead neutrophils, early phagocytosis of dead cells by macrophages at infarct border. Within 7-10 days there is well-developed phagocytosis of dead cells and GRANULATION TISSUE appears at margins

Question 64

Gross features and light microscope findings within 10-14 days of acute MI

Answer 64

Gross findings: red-gray depressed infarct borders Light mico: well-established granulation tissue with NEW BLOOD VESSELS and collagen deposition

Question 65

Gross features and light microscope findings within 2-8 weeks of acute MI

Answer 65

Gross findings: gray-white scar, progressive from border toward core of infarct Light micro: increased collagen deposition with decreased cellularity

Question 66

How long does it take for dense collagenous scarring to be complete after acute MI?

Answer 66

>2 months

Question 67

After acute MI, it takes 24+ hours to see _____ necrosis, _____ nuclei, and loss of cross ______

Answer 67

Coagulative; pyknotic; striations

Question 68

Areas surrounding necrosis following MI can rupture, causing blood to fill the pericardial sac leading to ____ ____ and further decreased heart function

Answer 68

Cardiac tamponade

Question 69

Timeline for PMNs, macrophages, and granulation tissue to form after MI

Answer 69

3-4 days = PMNs 7-10 days = macrophages 10 days = granulation tissue

Question 70

Gross findings of hemorrhage and Contraction bands seen on light micro are signs of ____ injury following MI

Answer 70

Reperfusion

Question 71

Lab evaluation of an MI consists of measuring the blood levels of proteins that leak out of irreversibly damaged myocytes. The most sensitive and specific biomarkers of myocardial damage are ____ and _____. ______ can also be used

Answer 71

cTnT and cTnI; CK-MB

Question 72

T/F: the MB form of creatine kinase (CK-MB) is sensitive but not specific, since it can also be elevated after skeletal muscle injury

Answer 72

True [while MM homodimers are found predominantly in cardiac and skeletal muscle, and BB homodimers in brain, lung, and many other tissues, MB heterodimers are principally localized to cardiac muscle, but there is still some in skeletal muscle, albeit low amounts]

Question 73

Time to elevation, peak, and return to normal of cardiac biomarkers/enzymes following MI

Answer 73

Time to elevation of CKMB, cTnT, and cTnI is 3-12 hours CKMB and cTnI peak at 24 hours CKMB returns to normal in 48-72 hours cTnI returns to normal in 5-10 days cTnT returns to normal in 5-14 days

Question 74

Half of MI deaths occur within 1 hr of onset, and are usually secondary to ________

Answer 74

Arrhythmia [arrhythmia can be a longer-term complication of MI, depending on site and extent of lesion; can result from permanent damage to the conducting system, or from myocardial “irritability” following the infarct]

Question 75

Complications of MI other than arrhythmia

Answer 75

Contractile dysfunction Fibrinous pericarditis Myocardial rupture Infarct expansion Ventricular aneurysm

Question 76

Myocardial rupture is a complication of MI that typically requires a _____ infarct. It occurs 2-4 days post MI, when inflammation and necrosis have weakened the wall. Risk factors include increased age, large transmural anterior MI, first MI, and absence of ____ hypertrophy

Answer 76

Transmural; LV

Question 77

Describe process of infarct expansion

Answer 77

Muscle necrosis —> weakening, stretching, and thinning of the wall Mural thrombus is often seen

Question 78

Describe ventricular aneurysm as a complication of MI

Answer 78

Late complication of large transmural infarcts with early expansion Composed of thinned wall of scarred myocardium Also associated with mural thrombus Rupture does NOT usually occur